This is a competing renewal application for an environmental pathology training program for 6 pre-doctoral (Ph.D. and M.D./Ph.D. degree) and 3 postdoctoral fellows. Since the inception of the training program in 1982, 53 pre-doctoral students and 31 postdoctoral fellows have been trained. These trainees have been recruited to academia, government and industry. A total of 20 highly interactive faculty members from 6 different clinical and basic research departments in the UVM College of Medicine (COM) participate in the program. All have funded research programs and are internationally recognized in disciplines related to mechanisms of action of environmental agents and pathology of environmental diseases. The program emphasizes courses on mechanisms and techniques to study the pathogenesis of environmental diseases and translational studies in human populations. Trainees gain research and laboratory experience in cell and tissue imaging, animal models of disease, and modern techniques in molecular biology including microarrays, bioinformatics, and proteomics. Faculty and trainees interact in a seminar series jointly sponsored with the NCI-funded Vermont Cancer Center (VCC), on research committees of fellows, and in Program Project grants directed by faculty on: 1) cell signaling in lung and pleural injury by inhaled particles and reactive oxygen species (ROS) (Mossman); 2) mechanisms of DNA damage and repair in skin cancers (Wallace); and 3) cell signaling and death pathways in immune diseases and in T-cell differentiation (Budd). State of the art facilities include a Microscopy Imaging Center, DNA Sequencing Facility in the VCC that features a TaqMan instrument, software for real-time quantitative PCR and Affymetrix gene arrays, a Bioinformatics Core supported through funds from the NCI, EPSCOR Program (DOE) , IDeA program (NIH) and the Howard Hughes Medical Institute, a UVM Protein Core Facility, a transgenic mouse facility, a small animal inhalation facility for particles and gases located in the Civil and Environmental Engineering Department, and a mass spectrometry facility in the Department of Chemistry. The Pathology Department also features a multi-user interactive Experimental Pathology Laboratory, aiding basic and clinical researchers within the department and COM. In alignment with the mission and strategic plan of the NIEHS, the investigators' goals are: 1) to expand the role of clinical research in environmental health sciences; 2) to understand the basic mechanisms of environmental toxic agents in the context of human disease; 3) to build integrated environmental health research programs at the University and through collaborations with other institutions; 4) to improve and expand community linked environmental research; 5) to develop sensitive biomarkers of adverse environmental exposures; and 6) to develop and train the next generation of environmental health science researchers. BACKGROUND This is a competing continuation application for renewal of this training program which has been funded for the past 25 years. The goals of the program have changed to bring it into better alignment with the revised mission and strategic plan of the NIEHS. Structurally, the current proposal seeks a change in the mix of pre-doctoral and postdoctoral slots from the current seven and two, respectively, to six and three, also fitting with the recommendations of NIEHS. The short term training slots for medical students, which were largely unfilled during the past term of this program, have been deleted from the current application.